Redox Biology
·
2024
·
IF 10.7
Bi-Xin Xu,Tian-Yu Hu,Jin-Biao Du,Tao Xie,Ya-Wen Xu,Xin Jin,Si-Tao Xu,Hao-Wen Jin,Guangji Wang,Jiankun Wang,Le Zhen
Redox-responsive hydropersulfide prodrugs are designed to enable a more controllable and efficient hydropersulfide (RSSH) supply and to thoroughly explore their biological and therapeutic applications in oxidative damage. To obtain novel activation patterns triggered by redox signaling, we focused on NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1), a canonical antioxidant enzyme, and designed NQO1-activated RSSH prodrugs. We also performed a head-to-head comparison of two mainstream structural scaffolds with solid quantitative analysis of prodrugs, RSSH, and metabolic by-products by LC-MS/MS, confirming that the perthiocarbamate scaffold was more effective in intracellular prodrug uptake and RSSH production. The prodrug was highly potent in oxidative stress management against cisplatin-induced nephrotoxicity. Strikingly, this prodrug possessed potential feedback activation properties by which the delivered RSSH can further escalate the prodrug activation via NQO1 upregulation. Our strategy pushed RSSH prodrugs one step further in the pursuit of efficient release in biological matrices and improved druggability against oxidative stress.
研究领域:
药学
·
生物化学
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分子生物学
·
毒理学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Zimin Cai,Qin Wang,Jinzhuan Xu,Jia Zhou,Zhaohui Jiang,Di Pan,Yanyan Zhang,Ling Tao,Jianqing Peng,Yi Chen,Xiangchun Shen
Emphysema is a type of chronic obstructive pulmonary disease (COPD) usually leading to difficulty breathing. It is highly in need of effective interventions to prevent airspace damage and stretch. Herein, we studied the protective effect of 1,8-cineole (CIN) on porcine pancreatic elastase (PPE)-induced emphysema in mice via quantitative pulmonary administration. To overcome the volatility, instability and poor water solubility of CIN that limits its pharmacological activities in vivo , a hyaluronic acid (HA)-coated liposome was prepared to encapsulate CIN (Lipo/ [email protected] ), which facilitated the delivery of CIN to lung tissue and improved its therapeutic effect for emphysema. A Microsprayer Ⓡ aerosolizer was used to deliver free CIN and its liposomal preparations every other day for four weeks and evaluate the therapeutic effects on emphysema in mice. The results clearly showed that CIN significantly reduced the level of inflammation and oxidative stress, resulting in less lung cell apoptosis. Compared with the free CIN and Lipo/CIN, Lipo/ [email protected] exhibited superior protective effects on mice to prevent the PPE-induced emphysema. Furthermore, the therapeutic mechanisms were verified to be mainly mediated by Nrf2/NQO1 and NF-κB/IκBα pathways. In conclusion, quantitative pulmonary administration of CIN could alleviate the progression of emphysema and the therapeutic effects were further improved by the HA-coated liposome carrier.
研究领域:
药理学
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肺病学
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药物递送系统
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分子生物学
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产品关联
DOI
高影响因子
Food & Function
·
2022
·Vol. 13
·期 5
·2782-2790
·
IF 6.317
Zunli Ke,Si Tan,Haiyang Li,Shanshan Jiang,Yuping Li,Rui Chen,Mingxia Li
Nonalcoholic liver disease (NAFLD) is a pathological condition characterized by excessive fat deposition in the liver, and NAFLD usually has a close relationship with obesity or metabolic syndrome. Currently, oxidative stress is considered as an important risk factor in the progression of NAFLD, therefore, effective amelioration of oxidative stress has emerged as a promising way to improve NAFLD. Tangeretin is a natural compound having various pharmacological activities including antioxidation and hepatoprotection. However, whether tangeretin is able to improve NAFLD through reducing hepatic oxidative stress is rarely reported. In our work, the preventive effects of tangeretin on a NAFLD mouse model induced by a high fat (HF) diet were studied. The results exhibited that tangeretin supplementation observably slowed down NAFLD progression through alleviation of metabolic indexes such as glucose tolerance, serum lipid levels and inflammatory factors, hepatic oxidative stress as well as steatosis. qRT-PCR showed that tangeretin supplementation increased the nuclear factor erythroid-2-related factor 2 (Nrf2) expression and then upregulated the expression of its downstream factors including HO-1, GCLC, NQO1 and GSTA2. Furthermore, the expression of the hepatic nucleus, Nrf2, HO-1 and GCLC, was also seen to be significantly enhanced in WB analysis. Taken together, this study implies that tangeretin might alleviate NAFLD through lowering oxidative stress in the liver by partial modulation of the Nrf2 pathway. Our study provided theoretical support that tangeretin could be used as a dietary therapy for obesity related-NAFLD or related metabolic syndrome.
研究领域:
药理学
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肝病学
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代谢性疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Mingye Li,Yuyu Dong,Zheng Wang,Yanjun Zhao,Yujie Dai,Baoxin Zhang
Glucose-6-phosphate dehydrogenase (G6PD) is a promising target in cancer therapy. However, poor cellular uptake and off-target toxicity impeded the clinical translation of a canonical G6PD inhibitor (6-aminonicotinamide/6AN). Here, we report a prodrug strategy to address this issue. The tailored 6AN prodrug contains an azo-bearing protection moiety. The hydrophobic prodrug showed increased cellular uptake than 6AN and is vulnerable to hypoxia, resulting in NAD(P)H quinone dehydrogenase 1 (NQO1)-triggered cleavage of azo bonds. Intriguingly, the prodrug shows configuration-dependent anti-cancer potency. Despite the lower thermodynamic stability, the cis isomer showed enhanced cellular uptake compared to the trans counterpart due to the increased aqueous solubility. Moreover, the boosted potency of cis isomer compared to the trans isomer resulted from the enhancement of NOQ1-catalyzed 6AN release under hypoxia, a hallmark of solid tumors. The discovery of hypoxia-responsive 6AN prodrugs in the current work opens new avenues of G6PD-targeting cancer medicines via redox manipulation.
研究领域:
药学
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癌症研究
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药物递送系统
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氧化还原生物学
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产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2018
·
IF 1.857
Yue Li,Yujuan Fan,Huizong Su,Qian Wang,Guo-Fu Li,Yiyang Hu,Jian Jiang,Bo Tan,Furong Qiu
Tanshinone I (TSI) is a lipophilic diterpene in Salvia miltiorrhiza with versatile pharmacological activities. However, metabolic pathway of TSI in human is unknown.In this study, we determined major metabolites of TSI using a preparation of human liver microsomes (HLMs) by HPLC-UV and Q-Trap mass spectrometer. A total of 6 metabolites were detected, which indicated the presence of hydroxylation, reduction as well as glucuronidation.Selective chemical inhibition and purified cytochrome P450 (CYP450) isoform screening experiments revealed that CYP2A6 was primarily responsible for TSI Phase I metabolism. Part of generated hydroxylated TSI was glucuronidated via several glucuronosyltransferase (UGT) isoforms including UGT1A1, UGT1A3, UGT1A7, UGT1A9, as well as extrahepatic expressed isoforms UGT1A8 and UGT1A10. TSI could be reduced to a relatively unstable hydroquinone intermediate by NAD(P)H: quinone oxidoreductase 1 (NQO1), and then immediately conjugated with glucuronic acid by a panel of UGTs, especially UGT1A9, UGT1A1 and UGT1A8. Additionally, NQO1 could also reduce hydroxylated TSI to a hydroquinone intermediate, which was immediately glucuronidated by UGT1A1.The study demonstrated that hydroxylation, reduction as well as glucuronidation were the major pathways for TSI biotransformation, and six metabolites generated by CYPs, NQO1 and UGTs were found in HLMs and S9 subcellular fractions.
研究领域:
药理学
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代谢
·
药物代谢
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Min Luo,Dan Luo,Jie Liu,Huailing Wang,Xiaoyu Liu,Min Yang,Fangfang Tian,Suofu Qin,Yuying Li
Probiotics are living bacteria that provide health benefits to the host when consumed in sufficient quantities. However, the protective effect of the bioactive peptides isolated from the probiotics against benzo(α)pyrene (BaP) induced gastrointestinal injury has never been investigated. The current work used a bio-assay guided technique to identify-four new cyclic peptides in BaP-induced Caco-2 cell culture and mouse colitis model. Lactobacillus rhamnosus cycle (Thr-His-Ala-Trp) peptide-1 (LRCP-1) effectively inhibited BaP-induced epithelial cytokine over-release and intracellular ROS over-production. Simultaneously, LRCP-1 attenuated BaP-induced NAD (P)H: oxidases (NOXs), Matrix metalloproteinases (MMPs) over-expression, respectively. Furthermore, increased NAD (P)H: quinone oxidoreductase 1 (NQO1)/heme oxygenase-1 (HO-1)/nuclear factor E2-related factor 2 (Nrf2) expression and aryl hydrocarbon receptor (AhR) pathway activation induced by the BaP-exposure were also inhibited after the LRCP-1 treatment. Notably, LRCP-1 is a promising agent protecting gastrointestinal epithelial cells from BaP-induced inflammatory and oxidative damages.
研究领域:
胃肠病学
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免疫学
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分子生物学
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毒理学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·Vol. 35
·期 43
·2417743
·
IF 19
Junji Li,Gaohua Li,Pengfei Guan,Rikuan Tong,Haoyang Feng,Kai Ang,Zhen Kong,Zhaobo Zhu,Can Liu,Cheng Li,Hongliang Wu,Yongjian Sun
It is now understood that oxidative stress, characterized by an excess of reactive oxygen species (ROS) within growth plate injury sites, can impede cartilage repair through various mechanisms. Morinda officinalis (MO), a traditional Chinese herbal medicine, possesses potent antioxidant properties. Furthermore, extracellular vesicles (EVs) derived from plants exhibit comparable physical and chemical characteristics to their parent plants, along with favorable tissue permeability and biocompatibility. Herein, it develops a ROS-sensitive hydrogel by self-crosslinking two natural extracellular matrix (ECM)-derived components: polyvinyl alcohol (PVA) and chondroitin sulfate grafted with phenylboric acid (CSBA). The hydrogel is subsequently combined with MO-derived EVs (MO-EVs) to eliminate excess ROS from the damaged microenvironment and release MO-EVs as needed to facilitate growth plate damage healing. In vitro studies revealed that a CSBA-PVA hydrogel containing MO-EVs facilitated the restoration of chondrocyte mitochondrial function by activating the NRF2-HO-1/NQO1 pathway, thereby enhancing endogenous antioxidant capacity. Furthermore, in vivo results reveal that implantation of CSBA-PVA hydrogel loaded with MO-EVs significantly inhibited bone bridge development and facilitated cartilage restoration within the growth plate. CSBA-PVA@MO-EVs therapy brings huge prospects as a therapeutic approach, offering novel insights and therapeutic strategies for treating growth plate injuries.
研究领域:
生物医学工程
·
再生医学
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植物药理学
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氧化应激生物学
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软骨组织工程
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纳米医学
✓ 已验证
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Hongxin Tan,Na Li,Sicheng Shu,Ziyan Fan,Jie Deng,Jingjing Wu,Xu Zhou,Qi Huang,Xi Cao
Cancer immunotherapy has garnered significant attention for its ability to reinstate immune responses to eliminate cancer effectively. Among immune cells, neutrophils play a dual-edged sword role in cancer, and the selective activation of beneficial neutrophil populations and targeted inhibition of tumor-promoting neutrophils have shown significant potential in cancer therapy. Here, we developed a neutrophil mimic nanovehicle (Neutrosome) capable of targeting colorectal cancer mitochondria (MNeutrosome), which consists of active neutrophil membranes hybridized with mitochondria-targeting liposome loaded with β-Lapachone (Liposome@Lapa), which is proposed to induce immunogenic cell death (ICD) and modulate the immune microenvironment. Our findings demonstrate that MNeutrosome@Lapa selectively accumulates in colorectal cancer mitochondria and activates quinone oxidoreductase-1 (NQO1), leading to robust reactive oxygen species (ROS) production and subsequent cancer cell apoptosis. Notably, the unloaded MNeutrosome was shown to reduce neutrophil infiltration into tumor tissue, whereas MNeutrosome@Lapa reprogrammed tumor-associated neutrophils (TANs) from a pro-tumor N2 phenotype to an anti-tumor N1 phenotype, further contributing to immune modulation. Overall, MNeutrosome@Lapa demonstrated excellent biocompatibility and significant therapeutic efficacy and represents a promising therapeutic platform for CRC treatment.
研究领域:
癌症免疫治疗
·
纳米医学
·
肿瘤微环境
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免疫学
·
活性氧信号通路
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xiaoyu Wu,Chuanbo Ding,Xinglong Liu,Qiteng Ding,Shuai Zhang,Yue Wang,Chenran Xin,Hewei Wei,Rui Mao,Guiping Zhang,Ting Zhao,Wencong Liu
Wound healing in diabetic patients is often complicated by issues like inflammation, infection, bleeding, and fluid retention. To tackle these challenges, it is essential to create hydrogel dressings with anti-inflammatory, antibacterial, and antioxidative properties. This study aimed to synthesize Phlorizin-Liposomes (PL) through the thin-film dispersion method and integrate them into an oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMCS) hydrogel scaffold, resulting in an OSA/CMCS/PL (PLOCS) composite hydrogel via a Schiff base reaction. Characterization of the composite was performed using FTIR, TEM, and SEM techniques. The research assessed the swelling behavior, antibacterial effectiveness, and biocompatibility of the PLOCS composite hydrogel, while also investigating how PLOCS facilitates diabetic wound healing. The results demonstrated that PLOCS effectively controls drug release, possesses favorable swelling and degradation characteristics, and shows significant antioxidative properties along with in vitro biocompatibility. Histological analysis confirmed that PLOCS supports the proliferation of healthy epithelial tissue and collagen production. Western blotting indicated that PLOCS diminishes inflammation by inhibiting the TLR4/NF-κB/MyD88 pathway and activates Nrf2 to boost wound healing, increasing the levels of antioxidative enzymes such as HO-1, NQO1, and GCLC. In summary, PLOCS presents a promising new option for advanced wound dressings aimed at treating diabetic ulcers.
研究领域:
材料科学
·
生物医学工程
·
药剂学
·
伤口愈合
·
糖尿病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Chen Hui,Zheng Huizhen,Li Tiejun,Jiang Qihong,Liu Shulai,Zhou Xuxia,Ding Yuting,Xiang Xingwei
Oyster peptide (OP) has exhibited useful biological activities and can be used in multi-functional foods. OP has been reported to play a significant role in intestinal protection, but its specific mechanism is still not completely understood. The aim of this study was to analyze the potential effect of OP on oxidative damage of mice intestine induced by cyclophosphamide (Cy). The experimental results revealed that intragastric administration of OP significantly increased average bodyweight, improved ileum tissue morphology and villus structure, as well as increased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in oxidized mice serum and liver. The content of malondialdehyde (MDA) in the mice serum and liver homogenate was found to be markedly decreased. Moreover, OP significantly increased the relative mRNA expression levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), quinone oxidoreductase (NQO1) and heme oxidase-1 (HO-1) in ileum. Western-blot results indicated that prior administration of OP significantly up-regulated the Nrf2 production in ileum, and substantially decreased then Keap1 gene expression. In conclusion, intake of OP was found to markedly improve intestinal oxidative stress in vivo, and this effect was primarily mediated through the simulation of antioxidant Nrf2-Keap1 signaling pathway. This study is beneficial to the application of peptide nutrients in the prevention or mitigation of intestinal oxidative damage.
研究领域:
营养学
·
药理学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Shuai Wang,Yinghua Mao,Shu Rong,Guangquan Liu,Yongping Cao,Zhan Yang,Huanhuan Yu,Xinrui Zhang,Hongyue Fang,Zhipeng Cai,Yonghong Chen,Hao Huang,Hong Li
Chemodynamic therapy (CDT), employing metal ions to transform endogenous H2O2 into lethal hydroxyl radicals (•OH), has emerged as an effective approach for tumor treatment. Yet, its efficacy is diminished by glutathione (GSH), commonly overexpressed in tumors. Herein, a breakthrough strategy involving extracellular vesicle (EV) mimetic nanovesicles (NVs) encapsulating iron oxide nanoparticles (IONPs) and β-Lapachone (Lapa) was developed to amplify intracellular oxidative stress. The combination, NV-IONP-Lapa, created through a serial extrusion from ovarian epithelial cells showed excellent biocompatibility and leveraged magnetic guidance to enhance endocytosis in ovarian cancer cells, resulting in selective H2O2 generation through Lapa catalysis by NADPH quinone oxidoreductase 1 (NQO1). Meanwhile, the iron released from IONPs ionization under acidic conditions triggered the conversion of H2O2 into •OH by the Fenton reaction. Additionally, the catalysis process of Lapa eliminated GSH in tumor, further amplifying oxidative stress. The designed NV-IONP-Lapa demonstrated exceptional tumor targeting, facilitating MR imaging, and enhanced tumor suppression without significant side effects. This study presents a promising NV-based drug delivery system for exploiting CDT against NQO1-overexpressing tumors by augmenting intratumoral oxidative stress.
研究领域:
癌症研究
·
纳米技术
·
药物递送系统
·
生物医学工程
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Fang Liu,Yaru Li,Yao Li,Zheng Wang,Xin Li,Yancheng Liu,Yanjun Zhao
The clinical translation of the anticancer drug β -lapachone (LAP) has been limited by the narrow therapeutic window. Stimuli-responsive anticancer drug delivery systems have gained tremendous attention in recent years to alleviate adverse effects and enhance therapeutic efficacy. Here, we report a dual pH- and enzyme-responsive nanocarrier to address the above issue of LAP. In detail, the epigallocatechin gallate (EGCG) and ferric ions were employed to engineer nanoscale ferric ion-polyphenol complexes where LAP was physically encapsulated therein. The coordination bond between Fe 3+ and the catechol moiety of EGCG was sensitive to the low pH, enabling the triggered cargo release in the acidic endosomes/lysosomes. Afterward, the released LAP was activated by the overexpressed NAD(P)H: quinone oxidoreductase 1 (NQO1) and ferroptosis suppressor protein 1 (FSP1) in the tumor cells, followed by the generation of reactive oxygen species (ROS), and the induction of oxidative stress and apoptotic cell death. Meanwhile, EGCG could upregulate gasdermin E (GSDME), and ferric ions were involved in the Fenton reaction. Hence, EGCG and ferric ions could sensitize the toxicity of LAP through the induction of multiple cell death pathways ( e.g ., pyroptosis, ferroptosis, apoptosis, and necroptosis). The current work enlarged the LAP’s therapeutic window via controlled cargo release and vehicle sensitization.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
药物递送系统
·
细胞死亡机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）